Protection against cyclophosphamide-induced alopecia and inhibition of mammary tumor growth by topical 1,25-dihydroxyvitamin D3 in mice.
Twenty-one-day-old BALB/c mice were shaved on the back to synchronize hair growth. On day 30 or 31, when at least 90% of mice exhibited hair regrowth in the shaved area, 1,25(OH)2D3 was applied topically to the shaved area daily for 5 days. On the 6th day, cyclophosphamide (Cytoxan, CTX) was injected i.p. to induce hair loss in the shaved area. Alopecia was induced in a dose-dependent manner by CTX treatment within 1 to 2 weeks. This effect was reduced significantly if mice were pre-treated with 1,25(OH)2D3, though only slight protection was observed in female mice. Interestingly, this 1,25(OH)2D3-mediated protection against hair loss was attenuated in male mice but became more significant in female mice when they were inoculated with the EMT-6 murine mammary tumor prior to treatment. More importantly, topical treatment with 1,25(OH)2D3 alone was able to inhibit EMT-6 tumor growth in both male and female BALB/c mice. Furthermore, 1,25(OH)2D3 pre-treatment also augmented the anti-tumor effect of CTX. Our results demonstrate that topical application of 1,25(OH)2D3 can protect against CTX-induced alopecia both in tumor-free and in tumor-bearing mice in a sex-dependent manner. Moreover, 1,25(OH)2D3 was shown, either alone or in combination with CTX, to inhibit tumor growth.
Chen
G
G
Department of Molecular Biology, The Cleveland Clinic Foundation, OH 44195, USA. cheng@cesmtp.ccf.org
Baechle
A
A
Nevins
T D
TD
Oh
S
S
Harmon
C
C
Stacey
D W
DW
D000287:Administration, Topical; D000505:Alopecia / Q000517:prevention & control*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002117:Calcitriol / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects*; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D002117:Calcitriol